QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, August 16, 2006, 26(33):8531-8536; doi:10.1523/JNEUROSCI.0726-06.2006

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Related articles in J. Neurosci. Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (49) Citing Articles via Google Scholar Google Scholar Articles by Xi, Z.-X. Articles by Gardner, E. L. Search for Related Content PubMed PubMed Citation Articles by Xi, Z.-X. Articles by Gardner, E. L.

 Previous Article  |  Next Article 

Brief Communications
Cannabinoid CB₁ Receptor Antagonist AM251 Inhibits Cocaine-Primed Relapse in Rats: Role of Glutamate in the Nucleus Accumbens

Zheng-Xiong Xi, Jeremy G. Gilbert, Xiao-Qing Peng, Arlene C. Pak, Xia Li, and Eliot L. Gardner

Neuropsychopharmacology Section, Behavioral Neuroscience Research Branch, Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Department of Health and Human Services, Baltimore, Maryland 21224

Correspondence should be addressed to Zheng-Xiong Xi at the above address. Email: zxi{at}intra.nida.nih.gov

Blockade of cannabinoid CB₁ receptors has been reported to inhibit cocaine- or cocaine cue-induced reinstatement of drug seeking. However, the mechanisms underlying this action are poorly understood. Given the importance of dopamine, glutamate, and GABA in cocaine reward and relapse, we studied the effects of AM251 [N-(piperidin-1-yl)-5-(4-iodophonyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide], a novel highly selective CB₁ receptor antagonist, on cocaine-primed reinstatement of drug-seeking behavior and on cocaine-induced changes in extracellular DA, glutamate, and GABA in the nucleus accumbens (NAc) under reinstatement conditions. We found that systemic administration of AM251 selectively inhibited cocaine-induced, but not sucrose plus sucrose cue-induced, reinstatement of reward-seeking behavior. AM251 alone did not trigger reinstatement. Local perfusion of AM251 into the NAc or the dorsal striatum also inhibited cocaine-triggered reinstatement. AM251 alone dose dependently elevated NAc glutamate in a voltage-dependent Na⁺ channel-dependent manner. AM251 did not affect NAc DA or GABA. Pretreatment with AM251 dose dependently inhibited cocaine-induced increases in NAc glutamate but not in DA. Blockade of NAc metabotropic glutamate mGluR2/3 receptors by LY341495 [(2S)-2-amino-2-[(1S,2S)-2-carboxycycloprop-1-yl]-3-(xanth-9-yl) propanoic acid] slightly facilitated cocaine-enhanced glutamate release but blocked the antagonism of cocaine-induced reinstatement by AM251. These data suggest the following: (1) CB₁ receptors exert tonic inhibition over NAc glutamate release under cocaine-extinction conditions; (2) blockade of CB₁ receptors by AM251 inhibits cocaine-enhanced NAc glutamate release and cocaine-triggered reinstatement; and (3) these effects appear to be mediated by activation of presynaptic mGluR2/3 autoreceptors secondary to AM251-induced increase (disinhibition) of NAc glutamate release.

Key words: cocaine; dopamine; glutamate; mGluR2/3; AM251; cannabinoid; relapse

---

Received Feb. 17, 2006; revised June 15, 2006; accepted July 3, 2006.

Correspondence should be addressed to Zheng-Xiong Xi at the above address. Email: zxi{at}intra.nida.nih.gov

Related articles in J. Neurosci.:

This Week in The Journal

J. Neurosci. 2006 26: i. [Full Text]  

This article has been cited by other articles:

				L. Orio, S. Edwards, O. George, L. H. Parsons, and G. F. Koob A Role for the Endocannabinoid System in the Increased Motivation for Cocaine in Extended-Access Conditions J. Neurosci., April 15, 2009; 29(15): 4846 - 4857. [Abstract] [Full Text] [PDF]

				M. A. L. C. da Veiga, F. Fonseca Bloise, R. H. Costa-e-Sousa, L. L. Souza, N. A. d. S. Almeida, K. J. Oliveira, and C. C. Pazos-Moura Acute effects of endocannabinoid anandamide and CB1 receptor antagonist, AM251 in the regulation of thyrotropin secretion J. Endocrinol., November 1, 2008; 199(2): 235 - 242. [Abstract] [Full Text] [PDF]

				R. T. LaLumiere and P. W. Kalivas Glutamate Release in the Nucleus Accumbens Core Is Necessary for Heroin Seeking J. Neurosci., March 19, 2008; 28(12): 3170 - 3177. [Abstract] [Full Text] [PDF]

				B. Pan, C. J. Hillard, and Q.-s. Liu Endocannabinoid Signaling Mediates Cocaine-Induced Inhibitory Synaptic Plasticity in Midbrain Dopamine Neurons J. Neurosci., February 6, 2008; 28(6): 1385 - 1397. [Abstract] [Full Text] [PDF]

				A.-G. Corbille, E. Valjent, G. Marsicano, C. Ledent, B. Lutz, D. Herve, and J.-A. Girault Role of Cannabinoid Type 1 Receptors in Locomotor Activity and Striatal Signaling in Response to Psychostimulants J. Neurosci., June 27, 2007; 27(26): 6937 - 6947. [Abstract] [Full Text] [PDF]

				S. Caille, L. Alvarez-Jaimes, I. Polis, D. G. Stouffer, and L. H. Parsons Specific Alterations of Extracellular Endocannabinoid Levels in the Nucleus Accumbens by Ethanol, Heroin, and Cocaine Self-Administration J. Neurosci., April 4, 2007; 27(14): 3695 - 3702. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help